Phase 4
N=93
A Study to Learn if Recombinant Human Parathyroid Hormone [rhPTH(1-84)] Can Improve Symptoms and Metabolic Control in Adults With Hypoparathyroidism (BALANCE)
Hypoparathyroidism
Bottom Line
View on ClinicalTrials.gov: NCT03324880 ↗Enrolled (actual)
93
Serious AEs
12.9%
Results posted
Jun 2023
Primary outcome: Primary: Change From Baseline in Hypoparathyroidism Symptom Diary (HypoPT-SD) Symptom Subscale Score at Week 26 — -0.93; -1.46 score on a scale — p==0.003
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 4
- Interventions
- rhPTH (1-84) (Biological); Placebo (Biological)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Shire
- Primary completion
- May 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Hypoparathyroidism Symptom Diary (HypoPT-SD) Symptom Subscale Score at Week 26 |
-0.93; -1.46 | =0.003 sig |
| SECONDARY Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Week 26 |
4.4; 15.0 | <0.001 sig |
| SECONDARY Change From Baseline in Physical Component Summary (PCS) Derived From 36-Item Short Form Health Survey Version 2 (SF-36v2) Scores at Week 26 |
4.404; 8.646 | =0.015 sig |
| SECONDARY Change From Baseline in Hypoparathyroidism Symptom Diary (HypoPT-SD) Impact Subscale Score at Week 26 |
-0.36; -0.69 | =0.002 sig |
| SECONDARY Change From Baseline in Individual Hypoparathyroidism Symptom Diary (HypoPT-SD) Impact Items Score at Week 26 |
-0.39; -0.68; -0.35; -0.71; -0.39; -0.76 | =0.013 sig |
| SECONDARY Change From Baseline in Hypoparathyroidism Symptom Diary (HypoPT-SD) Symptom Item Anxiety (Item 8) Score at Week 26 |
-0.79; -1.35 | =0.004 sig |
| SECONDARY Change From Baseline in Hypoparathyroidism Symptom Diary (HypoPT-SD) Symptom Item Sadness or Depression (Item 9) Score at Week 26 |
-0.76; -1.30 | =0.004 sig |
| SECONDARY Change From Baseline in Individual Hypoparathyroidism Symptom Diary (HypoPT-SD) Symptom Item Scores at Week 26 |
-0.91; -1.47; -1.04; -1.58; -0.89; -1.37 | =0.006 sig |
| SECONDARY Number of Participants With Response at Week 26 [Early Termination (ET)] |
24; 25 | — |
| SECONDARY Change From Baseline in the Most Bothersome Symptom Score at Week 26 |
-0.87; -1.77 | <0.001 sig |
| SECONDARY Change From Baseline in Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) Perceived Cognitive Impairments (PCI) Score at Week 26 |
2.7; 4.8 | =0.024 sig |
| SECONDARY Change From Baseline in Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) Impact on Quality of Life (QoL) Score at Week 26 |
2.7; 4.8 | =0.024 sig |
| SECONDARY Change From Baseline in Individual Domains of 36-Item Short Form Health Survey Version 2 (SF-36v2) at Week 26 |
4.194; 11.404; 3.515; 9.061; 3.719; 11.576 | =0.001 sig |
| SECONDARY Change From Baseline in Mental Component Summary (MCS) Score of 36-Item Short Form Health Survey Version 2 (SF-36v2) at Week 26 |
4.297; 12.597 | <0.001 sig |
| SECONDARY Change From Baseline in Work Productivity and Activity Impairment Questionnaire: Hypoparathyroidism (WPAI: Hypoparathyroidism) Score at Week 26 |
2.30; 5.43; -11.7; -26.3; -11.17; -26.08 | =0.627 |
| SECONDARY Change From Baseline in Scores of Patient's Assessment of Overall Health Status Using Patient Global Impression of Severity (PGI-S) at Week 26 |
-0.8; -1.4 | =0.010 sig |
| SECONDARY Change From Baseline in Scores of Patient's Assessment of Overall Health Status Using Patient Global Impression of Change (PGI-C) at Week 26 |
-0.6; -1.7 | — |
| SECONDARY Change From Baseline in In-Clinic Neurocognitive Assessment Scores at Week 24 |
0.03; 0.05; 0.02; 0.04; 0.12; 0.13 | =0.516 |
| SECONDARY Change From Baseline in At-Home Neurocognitive Assessment Scores at Week 26 |
-0.01; -0.01; -0.01; 0.00; 0.08; 0.09 | =0.582 |
| SECONDARY Change From Baseline in 24-hour Urine Calcium Excretion at Week 26 |
-1.99; 0.11 | =0.991 |
| SECONDARY Change From Baseline in Serum Phosphate Level at Week 26 |
0.030; -0.145 | <0.001 sig |
| SECONDARY Change From Baseline in Doses of Active Vitamin D at Week 26 |
-5.65; -1.57 | =0.810 |
| SECONDARY Change From Baseline in Doses of Calcium Supplements at Week 26 |
-44.3; -375.6 | =0.007 sig |
| SECONDARY Change From Baseline in Albumin-corrected Serum Calcium Control at Week 26 |
-0.033; 0.090 | — |
| SECONDARY Number of Participants Who Achieve Composite Criteria for Albumin-corrected Serum Calcium Concentration, Active Vitamin D Dose and Oral Elemental Calcium Supplement Dose at Week 26 |
6; 21 | — |
| SECONDARY Change From Baseline in Bone Turnover Marker Bone Specific Alkaline Phosphatase at Week 26 |
0.69; 23.03 | <0.001 sig |
| SECONDARY Change From Baseline in Bone Turnover Marker Type I Collagen C-Telopeptides at Week 26 |
-5.0; 780.5 | <0.001 sig |
| SECONDARY Change From Baseline in Bone Turnover Marker Osteocalcin and Procollagen 1 N-Terminal Propeptide at Week 26 |
-0.88; 55.55; 1.95; 228.52 | <0.001 sig |
| SECONDARY Number of Participants With Treatment Emergent Adverse Events (TEAEs) |
46; 41 | — |
Summary
Recombinant human parathyroid hormone, also known as if rhPTH(1-84), is a medicine to treat people with Hypothyroidism. The main aim of this study is to learn if rhPTH(1-84) can improve symptoms in adults with hypoparathyroidism.
In this study, participants will receive 1 of 2 treatments: rhPTH(1-84) or a placebo. A placebo looks like the medicine being studied but does not have medicine in it. In this study, the placebo will be a standard treatment which is either active Vitamin D, or active Vitamin D with calcium. Active Vitamin D is a form of vitamin D that has a faster effect on the body. These treatments will be given as a daily injection just under the skin. Participants will not know which treatment they received, nor will their study doctors. This is to help make sure the results are more reliable. All participants will also take active vitamin D and calcium supplements during treatment.
Participants will record their symptoms in a tool called the hypoparathyroidism symptom diary. This tool is used to assess symptoms and their impact and will give an overall score for each participant.
The study doctors will also check for side effects from the study treatments.
After treatment, researchers will check if there is any difference in the diary scores between the 2 treatment groups. A difference in score means there is a difference in symptoms and their impact. From this, researchers will learn if symptoms have improved for participants treated with rhPTH(1-84) compared with those treated with placebo.
Eligibility Criteria
Inclusion Criteria
- Has an understanding, ability, and willingness to fully comply with study procedures and restrictions.
- Is able to voluntarily provide a signed and dated informed consent form before any study-related procedures are performed.
- Is an adult male or female 18 to 85 years of age, inclusive.
- In participants 18-25 years of age, has radiological evidence of epiphyseal closure based on bone age X-ray (single posteroanterior X-ray of left wrist and hand) before randomization.
- Has chronic hypoparathyroidism with onset 12 months or more before screening. The diagnosis of hypoparathyroidism is established based on hypocalcemia in the setting of inappropriately low serum PTH levels.
- During the Week -3 screening visit, the participant reports by history at least 2 of the following symptoms related to hypoparathyroidism occurring within the 2 weeks before Week -3 visit: muscle cramps, muscle spasms or twitching, tingling, numbness, heaviness in arms or legs, physical fatigue, or slowed or confused thinking (brain fog).
- The participant must have a Hypoparathyroidism Symptom Diary (HPT-SD) symptom subscale Sum Score of greater than or equal to (>=) 10 during the 14-day period immediately prior to the baseline (Week 0) visit (Day -14 to Day -1). In addition, the participant must have at least 4 HPT-SD diaries completed in the first 7 day period and at least 4 HPT-SD diaries completed in second 7 day period.
- Must be treated with active vitamin D (calcitriol or alfacalcidol) alone or in conjunction with calcium supplements for at least 4 months prior to the screening visit.
- The participant must be taking >= 0.5 microgram (mcg)/day of calcitriol or >=1.0 mcg/day of alfacalcidol.
- If the participant is treated with a lower dose of active vitamin D the participant must also be taking calcium supplements of at least 800 milligrams per day (mg/day) of elemental calcium.
- Has serum thyroid-stimulating hormone (TSH) results within normal laboratory limits at screening for all participants not receiving thyroid hormone replacement therapy. For participants on thyroid hormone replacement therapy, the thyroid hormone dose must have been stable for at least 4 weeks before screening, and serum TSH level must be within the central laboratory normal range. A serum TSH level below the lower limit of the normal range but not undetectable in participant treated with thyroid hormone may be allowed if there is no anticipated need for a change in thyroid hormone dose during the trial.
- Has serum 25-hydroxyvitamin D levels >=50 nmol/L (nanomoles per liter) (20 nanograms per milliliter [ng/mL]) and less than ( ) 30 milliliter per minute per 1.73 square meters (ml/min/1.73m^2).
- Prior to randomization, is able to perform daily SC self-injections of study medication (or have a designee perform injection) via a multidose injection pen into the thigh.
- Willing to use oral active vitamin D and calcium supplements provided for the study unless directed to remain on the supplements used prior to enrollment in the current study by the investigator after consultation with the medical monitor.
- With regard to female participants: women who are postmenopausal (12 consecutive months of spontaneous amenorrhea and age >= 51 years) and women who are surgically sterilized can be enrolled. Women of childbearing potential must have a negative pregnancy test at randomization and be willing to comply with any applicable contraceptive requirements of the protocol and pregnancy testing for the duration of the study.
Exclusion Criteria
- History of hypoparathyroidism resulting from a known activating mutation in the CaSR gene or impaired responsiveness to PTH (pseudohypoparathyroidism).
- Any disease that might affect calcium metabolism or calcium-phosphate homeostasis other than hypoparathyroidism, such as poorly controlled hyperthyroidism; Paget disease; type 1 diabetes mellitus or poorly controlled type 2 diabetes mellitus; severe and chr
Data sourced from ClinicalTrials.gov (NCT03324880). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.